Pathways for pain therapy

In vivo optogenetic interrogation and manipulation of spinal cholinergic pathways for pain therapy

Chronic pain continues to be the single most common cause of disability that impairs the quality of life, accruing enormous socio-economic costs. In the look for novel and alternative therapies, our project focuses on cholinergic analgesia. Endogenous acetylcholine modulates nociceptive transmission in the spinal cord, and is involved in the analgesic effects of clonidine and morphine. We have recently identified its most probable source in the spinal cord of rodents and primates. Our project now aims elucidating the mode of action of this transmitter by studying spinal cholinergic neurons in vivo, in intact preparations and in relevant contextual frameworks. This requires the development of novel fibre-optics technologies that will enable to a) determine the role of specific neuronal pathways and b) test drug action in vivo. Our project will improve our understanding of the spinal nociceptive network. In addition, because clinically relevant analgesics such as morphine, clonidine or atropine involve the release of endogenous acetylcholine at the spinal level, identifying the source and mode of action of this acetylcholine is expected to enable refining existing therapies and developing new ones.